This project will investigate how neurochemical signals interact within the SCN to synchronize circadian rhythms in behavior with the day-night cycle. Since disorders of the circadian timing system have been linked to a variety of mental illnesses, understanding the neurobiology of circadian rhythms should lead to the development of new treatments for these diseases. At least three different afferent projections of the SCN are involved in the photic entrainment of circadian rhythms. The RHT is a direct projection from the retina that is necessary and sufficient for entrainment. Projections from the raphe and the intergeniculate leaflet to the SCN also influence entrainment although they do not provide input necessary for the entrainment process. The neurochemical signals contained in these afferent projections as well as in neurons intrinsic to the SCN interact in a complex manner to control photic entrainment. The long-term goal of this project is to define the neurochemical basis of the entrainment of circadian rhythms by defining how photic information is communicated to and processed within the SCN. Specific Aim I will test the hypothesis that an EAA is a neurotransmitter which communicates photic information to the SCN through the RHT. Since the investigator has been able to demonstrate that injection of an EAA agonist (i.e., NMDA) into the SCN in vivo can mimic the phase shifting effects of light, it will be possible to resolve a significant discrepancy about this hypothesis. Specific Aim 2 will test the hypothesis that substance P, which appears to be contained in the RHT, contributes to the entrainment by modulating the activity of EAAs in the SCN. Specific Aim 3 will investigate how the phase shifting effects of light are influenced by intrinsic SCN circuits and by afferent projections of the SCN. Specifically, the investigator will test the hypothesis that GABA, serotonin and NPY inhibit the phase shifting effects of light by inhibiting the phase shifting effects of EAAs and/or substance P in the SCN.